Advertisement

Long-term childhood outcomes for babies born at term who were exposed to antenatal corticosteroids

      Background

      Antenatal corticosteroids improve neonatal outcomes when administered to infants who are at risk of preterm delivery. Many women who receive antenatal corticosteroids for threatened preterm labor proceed to deliver at term. Thus, long-term outcomes should be evaluated for term-born infants who were exposed to antenatal corticosteroids in utero.

      Objective

      This study aimed to compare long-term outcomes between term-born children aged ≥5 years who were born to women who received antenatal corticosteroids for threatened preterm labor and children whose mothers were also evaluated for threatened preterm labor but did not receive antenatal corticosteroids.

      Study Design

      We performed a retrospective cohort study of children born at ≥37 weeks’ gestation, aged ≥5 years, and born to mothers diagnosed with threatened preterm labor during pregnancy. The primary exposure of interest was receiving antenatal corticosteroids. Among the collected childhood medical conditions, the primary outcome of interest was a diagnosis of asthma.

      Results

      Of the 3556 term-born children aged ≥5 years, 629 (17.6%) were exposed to antenatal corticosteroids (all betamethasone), and 2927 (82.3%) were controls whose mothers were evaluated for threatened preterm birth but did not get antenatal corticosteroid injections. Women receiving antenatal corticosteroids had higher rates of maternal comorbidities (diabetes mellitus, hypertension; P≤.01). Antenatal corticosteroid-exposed children had no difference in diagnosis of asthma (12.6% vs 11.6%), attention deficit disorder, or developmental delay (P=.47, .54, and .10, respectively). Controlling for maternal and neonatal characteristics, asthma was not different between those exposed to antenatal corticosteroids and controls (odds ratio, 1.05; 95% confidence interval, 0.79–1.39). The odds of the child’s weight percentile being <10% were increased for antenatal corticosteroid-exposed children born at term (odds ratio, 2.00; 95% confidence interval, 1.22–3.25).

      Conclusion

      Children born at term who were exposed to antenatal corticosteroids may have increased odds of being in a lower growth percentile than those not exposed. However, rates of diagnoses such as asthma, developmental delay, and attention deficit disorders were not different.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Committee on Obstetric Practice
        Committee opinion No. 713: antenatal corticosteroid therapy for fetal maturation.
        Obstet Gynecol. 2017; 130: e102-e109
        • Liggins G.C.
        • Howie R.N.
        A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants.
        Pediatrics. 1972; 50: 515-525
        • McGoldrick E.
        • Steward F.
        • Parker R.
        • Dalziel S.R.
        Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.
        Cochrane Database Syst Rev. 2020; 3: CD004454
        • Jobe A.H.
        • Goldenberg R.L.
        Antenatal corticosteroids: an assessment of anticipated benefits and potential risks.
        Am J Obstet Gynecol. 2018; 219: 62-74
        • Busada J.T.
        • Cidlowski J.A.
        Mechanisms of glucocorticoid action during development.
        Curr Top Dev Biol. 2017; 125: 147-170
        • Paules C.
        • Pueyo V.
        • Martí E.
        • et al.
        Threatened preterm labor is a risk factor for impaired cognitive development in early childhood.
        Am J Obstet Gynecol. 2017; 216: 157.e1-157.e7
        • Dalziel S.R.
        • Rea H.H.
        • Walker N.K.
        • et al.
        Long term effects of antenatal betamethasone on lung function: 30 year follow up of a randomised controlled trial.
        Thorax. 2006; 61: 678-683
        • Smolders-de Haas H.
        • Neuvel J.
        • Schmand B.
        • Treffers P.E.
        • Koppe J.G.
        • Hoeks J.
        Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12-year follow-up.
        Pediatrics. 1990; 86: 65-70
        • Bandyopadhyay A.
        • Slaven J.E.
        • Evrard C.
        • Tiller C.
        • Haas D.M.
        • Tepper R.S.
        Antenatal corticosteriods decrease forced vital capacity in infants born fullterm.
        Pediatr Pulmonol. 2020; 55: 2630-2634
        • McKinzie A.H.
        • Yang Z.
        • Teal E.
        • et al.
        Are newborn outcomes different for term babies who were exposed to antenatal corticosteroids?.
        Am J Obstet Gynecol. 2021; 225: 536.e1-536.e7
        • Golichowski A.M.
        • McDonald C.J.
        • Tierney W.M.
        • et al.
        Managing perinatal data with the Regenstrief medical record system.
        J Ambul Care Manage. 1992; 15: 40-53
        • McDonald C.J.
        • Overhage J.M.
        • Tierney W.M.
        • et al.
        The Regenstrief Medical Record System: a quarter century experience.
        Int J Med Inform. 1999; (54:225–53)
      1. World Heatlh organization growth curves. Accessed through Centers for Disease Control website. Available at: https://www.cdc.gov/growthcharts/who_charts.htm#The%20WHO%20Growth%20Charts. Accessed February 1, 2021.

        • Centers for Disease Control and Prevention
        Most recent national asthma data.
        2021 (Available at:) (Accessed February 1, 2021)
        • Jobe A.H.
        Animal models of antenatal corticosteroids: clinical implications.
        Clin Obstet Gynecol. 2003; 46: 174-189
        • Wapner R.
        Long term follow-up of infants receiving single vs repeat courses of antenatal corticosteroids (ACS) from the MFMU RCT.
        Am J Obstet Gynecol. 2006; 195: S2
        • Wapner R.J.
        • Sorokin Y.
        • Thom E.A.
        • et al.
        Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy.
        Am J Obstet Gynecol. 2006; 195: 633-642
        • Crowther C.A.
        • Middleton P.F.
        • Voysey M.
        • et al.
        Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: an individual participant data meta-analysis.
        PLoS Med. 2019; 16: e1002771
        • Abbasi S.
        • Hirsch D.
        • Davis J.
        • et al.
        Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome.
        Am J Obstet Gynecol. 2000; 182: 1243-1249
        • Delisle H.
        [Foetal programming of nutrition-related chronic diseases].
        Sante. 2002; 12: 56-63
        • Asztalos E.
        • Murphy K.
        • Willan A.R.
        • et al.
        Multiple Courses of Antenatal corticosteroids for peeterm birth study: 5-year outcomes (MACS-5).
        JAMA Pediatr. 2013; 167: 1102-1110
        • Asztalos E.V.
        Antenatal corticosteroids are currently used excessively and more stringent controls on their use should be established: FOR: the use of antenatal corticosteroids should be restricted if we are to avoid causing harm.
        BJOG. 2016; 123: 1787
        • Räikkönen K.
        • Gissler M.
        • Kajantie E.
        Associations between maternal antenatal corticosteroid treatment and mental and behavioral disorders in children.
        JAMA. 2020; 323: 1924-1933
        • Khalife N.
        • Glover V.
        • Taanila A.
        • Ebeling H.
        • Järvelin M.R.
        • Rodriguez A.
        Prenatal glucocorticoid treatment and later mental health in children and adolescents.
        PLoS One. 2013; 8: e81394
        • Romero R.
        • Erez O.
        • Maymon E.
        • Pacora P.
        Is an episode of suspected preterm labor that subsequently leads to a term delivery benign?.
        Am J Obstet Gynecol. 2017; 216: 89-94
        • Espinoza J.
        • Kusanovic J.P.
        • Kim C.J.
        • et al.
        An episode of preterm labor is a risk factor for the birth of a small-for-gestational-age neonate.
        Am J Obstet Gynecol. 2007; 196: 574.e1-574.e5
        • Campbell M.K.
        • Cartier S.
        • Xie B.
        • Kouniakis G.
        • Huang W.
        • Han V.
        Determinants of small for gestational age birth at term.
        Paediatr Perinat Epidemiol. 2012; 26: 525-533
        • Zoabi L.
        • Weintraub A.Y.
        • Novak L.
        • et al.
        Do patients who deliver at term after being hospitalized for preterm contractions have an increased risk for obstetrical complications?.
        Arch Gynecol Obstet. 2013; 288: 537-542
        • Romero R.
        • Espinoza J.
        • Kusanovic J.P.
        • et al.
        The preterm parturition syndrome.
        BJOG. 2006; 113: 17-42
        • Oros D.
        • Strunk M.
        • Breton P.
        • et al.
        Altered gene expression in human placenta after suspected preterm labour.
        Placenta. 2017; 55: 21-28
        • Schoorlemmer J.
        • Macías-Redondo S.
        • Strunk M.
        • et al.
        Altered DNA methylation in human placenta after (suspected) preterm labor.
        Epigenomics. 2020; 12: 1769-1782
        • Ashwood P.J.
        • Crowther C.A.
        • Willson K.J.
        • et al.
        Neonatal adrenal function after repeat dose prenatal corticosteroids: a randomized controlled trial.
        Am J Obstet Gynecol. 2006; 194: 861-867

      Linked Article

      • A dilemma of antenatal corticosteroids for long-term consequences
        American Journal of Obstetrics & GynecologyVol. 228Issue 1
        • Preview
          Antenatal corticosteroids (ACS) are known to accelerate fetal lung maturation and prevent preterm neonatal mortality, respiratory distress syndrome, and brain injury. The American College of Obstetricians and Gynecologists has expanded its recommendations for the use of ACS to late preterm and early term deliveries.1 Under such guidelines, the proportion of infants who are exposed to synthetic corticosteroids has substantially increased. In the setting of a large infant population being involved, it is imperative to evaluate the long-term safety of ACS, especially after a population-based cohort study that reported a hazard ratio of 1.47 of any mental or behavioral disorder in children born at term who were exposed to ACS.
        • Full-Text
        • PDF